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Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q152-aff1-only-recurrent-core

TBX21 (T-bet) - the Th1/NK master regulator, the third lymphoid gene in the Q152 AFF1-only core and the one that makes the B-lineage reading fail

also called T-bet · TBET · T-PET · TBLYM · T-box protein 21

TBX21, usually called T-bet, is the master switch for Th1 T cells and natural killer cells - not B cells. Its presence among the seventeen genes is what turns a tidy 'B-cell programme' story into an untidy 'lymphoid-ish' one, and it is the reason the statistical test had to use the broader lymphocyte gene set as well.

The same thing, for a scientist

TBX21 (Q9UL17, 535 aa) is the T-box transcription factor T-bet, the master regulator of Th1 differentiation and NK-cell maturation and a driver of IFNG. It is annotated to GO:0030098 lymphocyte differentiation but NOT to GO:0030183 B cell differentiation, and it is the single gene that separates those two pre-registered tests in Q152: L1 overlap is 2 (BLNK, POU2AF1) and L2 overlap is 3 (plus TBX21). Its promoter is occupied in 3 of 8 KMT2A::AFF1 samples of GSE252378 (p247, p279, p454) at 2.08-3.27x with the highest non-AFF1 value 1.64x, a margin of 1.27.

Go deeper
Why a T/NK regulator in an infant B-ALL deposit is a warning, not a finding

The intuitive reading of the Q152 core - POU2AF1, BLNK, WT1, TBX21 - is 'a lymphoid programme'. TBX21 is the member that makes that reading incoherent: T-bet is not expressed in normal B-cell development outside a small age-associated B-cell subset, and there is no published account of it as a KMT2A-fusion target. Its inclusion is better read as evidence that the four 'recognisable' genes are recognisable because they are famous, not because they belong together. A set of seventeen genes will almost always contain three the reader recognises; the pre-registered test exists precisely so that impression can be scored, and it scored negative once the null was activity-matched 2.

Facts and figures
uniprotQ9UL17
length AA535
gene symbolTBX21
hgnc symbolTBX21
chromosome17q21.32
promoter hg38chr17:47,732,235-47,734,235 (TSS 47,733,235, plus strand, NM_013351)
shown for fusionNO - nobody has published a KMT2A-fusion occupancy or knockdown experiment on TBX21 that this beat could find; TBX21 is named in 0 of the 2,857 existing node files of this graph.
relationship to existing entriesNamed by beat Q152 because its promoter sits in the 17-gene AFF1-only recurrent core of GSE252378. Q152's headline result is that that core is NOT more recurrence than a label permutation gives (p = 0.11). This entry therefore does NOT claim the gene is a KMT2A::AFF1 target; it exists because the gene is real biology in this disease and had no entry.
measurements
[
  {
    "quantity": "n_aff1_samples_occupied",
    "subject": "TBX21 2 kb promoter in the KMT2A::AFF1 arm of GSE252378",
    "value": 3,
    "units": "samples of 8",
    "n": 27,
    "universe": "27 GSE252378 KMT2A-fusion samples, two-antibody 2.0x plus per-library width-matched floor",
    "null": 2.73,
    "note": "p247, p279, p454; occupied calls 2.08-3.27x; 0 of 19 non-AFF1, highest non-AFF1 1.64x (R3595), margin 1.27"
  }
]
Still open
  1. Is TBX21 transcript detectable at all in these blasts? A promoter occupancy call on a gene that is not expressed would be the cleanest demonstration that the 2.0x rule reads something other than active transcription.
Every source behind this entry (2)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    TBX21 is a reviewed human UniProt entry, accession Q9UL17, 535 residues, T-box transcription factor TBX21, also known as T-cell-specific T-box transcription factor T-bet and TBLYM.

    UniProtKB Q9UL17 - T-box transcription factor TBX21 (Homo sapiens), reviewed · UniProt Consortium · UniProtKB/Swiss-Prot 2026
    What this evidence cannot show

    gene_exact:TBX21 returns one reviewed human record; no row in data/symbol-collisions.json (checked, 211 rows). 'T-bet' and 'TBET' are both in wide use and a symbol-only literature search under-counts.

    Evidence that argues against this (1)
    • T-bet is the far commoner name in the immunology literature and a symbol-only search under-counts; the zero mentions of TBX21 across 2,857 node files may partly reflect that this graph writes T-bet when it means TBX21, although a search for both found nothing. UniProt Consortium 2026
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset

    In GSE252378 the TBX21 2 kb promoter (hg38 chr17:47,732,235-47,734,235, plus-strand refGene TSS 47,733,235, NM_013351) is occupied in 3 of 8 KMT2A::AFF1 samples (p247, p279, p454) at 2.08-3.27x and 0 of 19 non-AFF1 samples, highest non-AFF1 1.64x in R3595, margin 1.27; TBX21 is annotated to GO:0030098 lymphocyte differentiation and not to GO:0030183 B cell differentiation, and is the one gene by which the two pre-registered overlap tests differ.

    Q152 per-core-gene occupancy, separation margins and pre-registered GO overlaps · Iqbal Lab oncofusion knowledge graph, beat Q152 · this project 2026
    What this evidence cannot show

    Q152's permutation null shows a 3-of-8 AFF1-exclusive pattern is within the chance range; and the activity-matched GO test that TBX21 contributes to returns p = 0.043 against a pre-registered 0.025 threshold.

    Evidence that argues against this (1)
    • TBX21's presence could be read the other way: if the occupancy calls are real, a fusion that switches on a T/NK master regulator in a B-lineage blast would be a lineage-infidelity finding of some interest, and this beat's negative statistical verdict does not exclude it. A paired transcript measurement would settle whether the promoter is doing anything. NCBI Gene Expression Omnibus 2024
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